PMID- 18922704
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20210109
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 17
IP  - 4
DP  - 2009 Apr
TI  - PGE2 signal via EP2 receptors evoked by a selective agonist enhances regeneration 
      of injured articular cartilage.
PG  - 529-38
LID - 10.1016/j.joca.2008.09.003 [doi]
AB  - OBJECTIVE: The effect of the prostaglandin E2 (PGE2) signal through prostaglandin 
      E receptor 2 (EP2) receptors on the repair of injured articular cartilage was 
      investigated using a selective agonist for EP2. METHODS: Chondral and 
      osteochondral defects were prepared on the rabbit femoral concave in both knee 
      joints, and gelatin containing polylactic-co-glycolic acid microspheres 
      conjugated with or without the EP2 agonist was placed nearby. Animals were 
      sacrificed at 4 or 12 weeks post-operation, and regenerated cartilage tissues and 
      subchondral structure remodeling were evaluated by histological scoring. The 
      quality of regenerated tissues was also evaluated by the immunohistochemical 
      staining of EP2, type II collagen, and proliferating cell nuclear antigen (PCNA). 
      As an evaluation of side effects, the inflammatory reaction of the synovial 
      membrane was analyzed based on histology and the mRNA expression of matrix 
      metalloproteinase3 (MMP3), tissue inhibitor of metalloproteinase 3 (TIMP3), and 
      interleukin-1 beta (IL-1 beta). Also, the activity of MMP3 and the amount of 
      tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein in joint fluid 
      were measured. RESULTS: In both models, the EP2 agonist enhanced the regeneration 
      of the type II collagen-positive tissues containing EP2- and PCNA-positive 
      chondrocytes, and the histological scale of regenerated tissue and subchondral 
      bone was better than that of on the control side, particularly at 12 weeks 
      post-operation. No inflammatory reaction in the synovial membrane was observed, 
      and no induction of pro-inflammatory cytokines was found in joint fluid. 
      CONCLUSION: Selective stimulation of the PGE2 signal through EP2 receptors by a 
      specific agonist promoted regeneration of cartilage tissues with a physiological 
      osteochondral boundary, suggesting the potential usefulness of this small 
      molecule for the treatment of injured articular cartilages.
FAU - Otsuka, S
AU  - Otsuka S
AD  - Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto 
      University, Kyoto, Japan.
FAU - Aoyama, T
AU  - Aoyama T
FAU - Furu, M
AU  - Furu M
FAU - Ito, K
AU  - Ito K
FAU - Jin, Y
AU  - Jin Y
FAU - Nasu, A
AU  - Nasu A
FAU - Fukiage, K
AU  - Fukiage K
FAU - Kohno, Y
AU  - Kohno Y
FAU - Maruyama, T
AU  - Maruyama T
FAU - Kanaji, T
AU  - Kanaji T
FAU - Nishiura, A
AU  - Nishiura A
FAU - Sugihara, H
AU  - Sugihara H
FAU - Fujimura, S
AU  - Fujimura S
FAU - Otsuka, T
AU  - Otsuka T
FAU - Nakamura, T
AU  - Nakamura T
FAU - Toguchida, J
AU  - Toguchida J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081014
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - C-Reactive Protein/metabolism
MH  - Cartilage, Articular/drug effects/*injuries/pathology/physiology
MH  - Cell Proliferation/drug effects
MH  - Dinoprostone/*physiology
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical/methods
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Rabbits
MH  - Receptors, Prostaglandin E/agonists/*physiology
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Regeneration/drug effects/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Synovial Fluid/metabolism
MH  - Synovial Membrane/drug effects/pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2008/10/17 09:00
MHDA- 2010/01/15 06:00
CRDT- 2008/10/17 09:00
PHST- 2008/04/13 00:00 [received]
PHST- 2008/09/02 00:00 [accepted]
PHST- 2008/10/17 09:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
PHST- 2008/10/17 09:00 [entrez]
AID - S1063-4584(08)00300-2 [pii]
AID - 10.1016/j.joca.2008.09.003 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2009 Apr;17(4):529-38. doi: 10.1016/j.joca.2008.09.003. 
      Epub 2008 Oct 14.